Influence of the Non-Linear Fitting Approach on JOSEF LISSNER LABORATORY FOR BIOMEDICAL IMAGING INSTITUTE FOR CLINICAL RADIOLOGY PROF. DR. MAXIMILIAN REISER Influence of the Non-Linear Fitting Approach on Intravoxel Incoherent Motion (IVIM) MRI: A Model Selection Study Moritz Schneider1, Michael Ingrisch1, Matthias Moser², Heidrun Hirner², Clemens Cyran², Konstantin Nikolaou², Maximilian Reiser² and Olaf Dietrich1 1Josef Lissner Laboratory for Biomedical Imaging, Institute for Clinical Radiology, LMU Ludwig Maximilian University of Munich, Munich, Germany 2Institute for of Clinical Radiology, LMU Ludwig Maximilian University of Munich, Munich, Germany Introduction Intravoxel incoherent motion (IVIM) MRI can be used to assess tissue microcapillary perfusion properties based on diffusion-weighted acquisitions by fitting a biexponential model function to the measured signal attenuation as a function of the diffusion weighting (b-value); the perfusion properties are reflected by the initial signal attenuation at small b-values between 0 and about 150 s/mm² [1,2]. Several strategies have been proposed for the fitting procedure including two-step linear-fit approaches applied to the logarithm of the signal attenuations or non-linear multi-parameter fitting using, e. g., the Levenberg-Marquardt algorithm. While the conventional fully biexponential model has 4 free parameters, including the initial signal at b-value 0, several studies use only the signal attenuation relative to this initial value (e. g. [3]), thus artificially discriminating, the measurements at b=0 and at higher b-values. Therefore, the aim of the present study is to use a model selection approach based on the Akaike information criterion (AIC)[4] to decide whether a biexponential model with 3 or 4 free parameters is more appropriate for typical IVIM data. Results Mean values and standard deviations of the model parameters are summarized in Table 1. In all 12 animals, the 3-parameter fit (B3) showed the highest Akaike weights ranging from 90.3% to 98.8%, and thus, is with very high probability the most appropriate model. The standard deviations of D* and f are slightly higher with B4 than with B3. The monoexponential models exhibit very low Akaike weights typically below 1%. Table 1: Mean values (std. dev.) of fit parameters and Akaike weights Model S0 (a.u) D (10-3mm²/s) D* (10-3mm²/s) f (%) Wakaike (%) M1 - 0.717 (0.128) 0.2 (0.6) M2 115 (77) 0.677 (0.113) 0.7 (1.7) B3 0.562 (0.104) 4.73 (2.69) 13.1 (3.3) 96.6 (3.0) B4 118 (79) 0.554 (0.101) 4.40 (2.75) 14.1 (4.3) 2.5 (2.4) The result of a voxelwise analysis of one rat is shown in Figure 2, in which the color-coded overlay over the tumor area in (a) represents the model with the highest Akaike weight for each voxel, the most dominant being B3 (purple). Figure 2(b)-(e) are the individual weight maps for every model; interestingly, both monoexponential models generate high weights at the tumor edge. Table 2 is a comparison of the resulting weights from the ROI and voxelwise analysis; the mono-exponential models M1 and M2 exhibit much higher weights when analyzed voxel-by-voxel. Materials and Methods 12 athymic nude rats with implanted breast carcinoma tumors were examined in a 3-Tesla whole-body MRI system (Magnetom Verio, Siemens Healthcare). IVIM measurements were performed with a single-shot EPI sequence (100×100 matrix; FoV 100×100mm²; 9 slices with thickness of 3 mm; TR/TE=2600/90ms; 8 averages; and 10 b-values from 0 to 1600 s/mm²). For ADC and IVIM evaluation, multi-slice regions of interest of homogeneous appearing tumor tissue (without necrosis areas) were defined. The signal attenuations were fitted with either a monoexponential (M): 𝑆 𝑏 = 𝑆 0 ∙ 𝑒 −𝑏𝐷 , or biexponential (B) model: 𝑆(𝑏)= 𝑆 0 𝑓∙ 𝑒 −𝑏 𝐷+𝐷∗ +(1−𝑓)∙ 𝑒 𝑏𝐷 , with a maximum of 4 free parameters: initial signal S0, (apparent) diffusion coefficient D, pseudo diffusion coefficient D*, perfusion fraction f. We compared 4 models with 1 (M1: D), 2 (M2: S0, D), 3 (B3: D, D*, f), or 4 (B4: S0, D, D*, f) free parameters (in M1 and B3, S0 is set to the measured value S(0)). An example for all 4 fits is shown in Fig. 1. [%] W 100 b M1 c M2 d B3 e B4 a Model ROI Voxel-by-Voxel M1 0.01% 13.18(22.29)% M2 0.02% 13.69(19.36)% B3 97.11% 70.12(32.63)% B4 2.86% 3.00(8.07)% Figure 2: Results of a voxelwise analysis. Colored overlay in (a) represents the model with the highest Akaike weight (M1: blue; M2: cyan; B3: purple; B4: red). (b)-(e) show the individual weight maps for each model M1-B4. Table 2: Comparison of the resulting Akaike weights from ROI and voxelwise (mean value and std. dev.) analysis of one animal. The quality of the fit and the appropriateness of the model were assessed using the AIC and the corresponding Akaike weights, which describe the probability that a certain model is appropriate for given data [4]. In addition, a voxelwise analysis of one rat was also performed resulting in parameter maps of the Akaike weights. Figure 1: Signal attenuation and fitted models; inlay plots show zoomed view of data at small b-values and MRI data Conclusions The evaluated tumor data show a clear biexponential attenuation (as confirmed by the low Akaike weights for the monoexponential models). The comparison of the models B3 and B4 based on the Akaike weights results in a very strong preference of the 3-parameter model. With a 4-parameter model, the fits are only marginally improved (in terms of the sum of squares of the differences between data and model); at the same time, the parameter standard deviations of D* and f increase slightly. When analyzed voxel-by-voxel, the increased weights of the monoexponential models M1 and M2 are likely to be induced by the higher noise level of a single voxel compared to a ROI, especially at the tumor edge. Nonetheless, the superiority of the 3-parameter model remains present. tumor ISMRM 2012, Melbourne Moritz.Schneider@med.uni-muenchen.de Made with Gnumeric and PMI 0.4 References: [1] Le Bihan D et al. Radiology 1988; 168: 497–505, [2] Koh D et al. AJR 2011; 196: 1351–1361, [3] Döpfert J et al. Magn Reson Imaging 2011; 29: 1053–1580, [4] Glatting G et al. Med Phys 2007; 34: 4285–4292